Before the siege of the city began, the Ottomans were at peace with the Byzantine Empire. The Empire by this time consisted only of the city of Constantinople itself, the rest having been gradually conquered in the previous decades and centuries. In the over 1000 years of the existence of the Empire, Constantinople had been besieged many times, but had been taken only once, during the Fourth Crusade. However, no enemy of Byzantium had ever specifically set out to conquer the Empire and actually succeeded in doing so. Mehmed planned on being the first.

Mehmed had a castle built outside the walls of Constantinople on the European side of the Bosporus, which would act as a base for the final assault on the city (this castle was called Rumeli Hisar, the "castle of Rome"). Meanwhile, Byzantine emperorConstantine XI tried to buy him off with gifts, but when Mehmed beheaded two of his ambassadors, Constantine finally began to prepare for war.

Constantine appealed to Western Europe for help, but Pope Nicholas V was unwilling to support the Empire after the failed Council of Basel. Some Venetians and Genoans did arrive, however. The Byzantine army itself totalled about 7000 men, 2000 of whom were foreign mercenaries. The city also had fourteen miles of walls, probably the strongest set of fortified walls in existence at the time. The Ottomans, on the other hand, had a much larger force, numbering around 100 000, including 20 000 Janissaries. Mehmed also built a fleet to besiege the city from the sea.

The Ottomans had a Hungarian engineer who was a specialist in the construction of cannons, which were still relatively new weapons. He built an enormous cannon, twenty-six feet in length and eight inches in diameter, which could fire a 1200-pound ball as far as one mile. Although the Byzantines also had cannons, they were much smaller and their recoil tended to damage their own walls.

Mehmed planned to attack the land walls from the west, the only part of the city not surrounded by water. His army encamped outside the city on Easter Monday, April 2, 1453. For seven weeks Mehmed's massive cannon fired on the walls, but it was unable to sufficiently penetrate them, and due to its extremely slow rate of reloading the Byzantines were able to repair most of the damage after each shot. Meanwhile, Mehmed's fleet could not enter the Golden Horn[?] due to the large chain the Byzantines had laid across the entrance. To circumvent this he built a road of greased logs across Galata[?] on the north side of the Golden Horn, and rolled his ships across. This succeeded in stopping the flow of supplies from Genoan ships and demoralizing the Byzantine defenders, but did not help in breaching the land walls.

Mehmed offered to raise the siege for an astronomical tribute that he knew the city would be unable to pay. When this was declined, Mehmed planned to overpower the walls by sheer force, knowing that the Byzantine defenders would be worn out before he ran out of troops. On the morning of May 29 the attack began. The first wave of attackers, the bashi-bazouks, were poorly trained and equipped, and were meant only to kill as many Byzantine defenders as possible. The second assault focused on a section of the Blachernae walls in the northwest part of the city, which had been partially damaged by the cannon; the attackers managed to break through, but were just as quickly pushed back out by the Byzantines. The Byzantines also managed to hold off an attack by the Janisseries, but the Genoan general in charge of the defense, Giovanni Giustiniani[?], was wounded in the attack, and the Greek troops began to panic.

Unfortunately, the Kerkoporta[?] gate in the Blachernae section had been left unlocked, and the Ottomans soon discovered this mistake. The Ottomans rushed in, and Constantine XI himself led the last defense of the city, dying in the ensuing battle in the streets.

The city was looted for three days, in accordance with the traditional punishment allotted on a city that had resisted a siege, but Mehmed restrained his troops out of respect for the ancient but now conquered empire. Mehmed was nicknamed "the Conqueror," and Constantinople, renamed Istanbul, became the new capital of the Ottoman Empire. Hagia Sophia was converted in a mosque, although the Greek Orthodox Church remained intact, and Gennadius Scholarius was appointed Patriarch of Constantinople. The last Byzantine state, the Empire of Trebizond, held out until 1461.

Many Greeks fled and found refuge in Italy, where they helped launch the Renaissance; those who stayed were mostly confined to the Phanar and Galata districts. The Phanariots, as they were called, often provided capable advisors to the Ottoman sultans, and were just as often seen as traitors by other Greeks.

Some scholars consider that the Middle Ages ended at the time of the Fall of Constantinople.

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